Regulation of the transcriptional activity of c-Fos by ERK: A novel role for the prolyl isomerase Pin1

Paula V Monje, Javier Hernández-Losa, Ruth J. Lyons, Maria D. Castellone, J. Silvio Gutkind

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Abstract

The activation of the activating protein-1 (AP-1) family of transcription factors, including c-Fos and c-Jun family members, is one of the earliest nuclear events induced by growth factors that stimulate extracellular signal-regulated kinases (ERKs). In the case of c-Fos, the activation of ERK leads to an increased expression of c-fos mRNA. In turn, we have recently shown that ERK phosphorylates multiple residues within the carboxyl-terminal transactivation domain (TAD) of c-Fos, thus resulting in its increased transcriptional activity. However, how ERK-dependent phosphorylation regulates c-Fos function is still poorly understood. In this regard, it has been recently observed that the prolyl isomerase Pin1 can interact with proteins phosphorylated on serine or threonine residues that precede prolines (pS/T-P), such as the transcription factors p53 and c-Jun, thereby controlling their activity by promoting the cis-trans isomerization of these pS/T-P bonds. Here, we found that Pin1 binds c-Fos through specific pS/T-P sites within the c-Fos TAD, and that this interaction results in an enhanced transcriptional response of c-Fos to polypeptide growth factors that stimulate ERK. Our findings suggest that c-Fos represents a novel target for the isomerizing activity of Pin1 and support a role for Pin1 in the mechanism by which c-Jun and c-Fos can cooperate to regulate AP-1-dependent gene transcription upon phosphorylation by mitogen-activated kinase (MAPK) family members.

Original languageEnglish
Pages (from-to)35081-35084
Number of pages4
JournalJournal of Biological Chemistry
Volume280
Issue number42
DOIs
StatePublished - Oct 21 2005

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Peptidylprolyl Isomerase
Extracellular Signal-Regulated MAP Kinases
Phosphorylation
Transcriptional Activation
Intercellular Signaling Peptides and Proteins
Transcription Factors
Chemical activation
Proteins
Mitogen-Activated Protein Kinase Kinases
Threonine
Transcription
Isomerization
Mitogens
Proline
Serine
Genes
Messenger RNA
Peptides

ASJC Scopus subject areas

  • Biochemistry

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Regulation of the transcriptional activity of c-Fos by ERK : A novel role for the prolyl isomerase Pin1. / Monje, Paula V; Hernández-Losa, Javier; Lyons, Ruth J.; Castellone, Maria D.; Gutkind, J. Silvio.

In: Journal of Biological Chemistry, Vol. 280, No. 42, 21.10.2005, p. 35081-35084.

Research output: Contribution to journalArticle

Monje, Paula V ; Hernández-Losa, Javier ; Lyons, Ruth J. ; Castellone, Maria D. ; Gutkind, J. Silvio. / Regulation of the transcriptional activity of c-Fos by ERK : A novel role for the prolyl isomerase Pin1. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 42. pp. 35081-35084.
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